Division of Cell and Molecular Biology & Center for Research of Diabetes, Metabolism and Nutrition, Third Faculty of Medicine, Charles University, Ruská 87, 100 00 Prague, Czech Republic.
Int J Mol Sci. 2017 Nov 2;18(11):2313. doi: 10.3390/ijms18112313.
It has been shown that saturated fatty acids (FAs) have a detrimental effect on pancreatic β-cells function and survival, leading to apoptosis, whereas unsaturated FAs are well tolerated and are even capable of inhibiting the pro-apoptotic effect of saturated FAs. Molecular mechanisms of apoptosis induction and regulation by FAs in β-cells remain unclear; however, mitogen-activated protein (MAP) kinase and endoplasmic reticulum (ER) stress signaling pathways may be involved. In this study, we tested how unsaturated oleic acid (OA) affects the effect of saturated stearic acid (SA) on the p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase (ERK) pathways as well as the ER stress signaling pathways during apoptosis induction in the human pancreatic β-cells NES2Y. We demonstrated that OA is able to inhibit all effects of SA. OA alone has only minimal or no effects on tested signaling in NES2Y cells. The point of OA inhibitory intervention in SA-induced apoptotic signaling thus seems to be located upstream of the discussed signaling pathways.
已经表明，饱和脂肪酸（FAs）对胰腺β细胞的功能和存活有不利影响，导致细胞凋亡，而不饱和 FAs 则耐受良好，甚至能够抑制饱和 FAs 的促凋亡作用。FA 诱导和调节β细胞凋亡的分子机制尚不清楚；然而，丝裂原活化蛋白（MAP）激酶和内质网（ER）应激信号通路可能参与其中。在这项研究中，我们测试了不饱和油酸（OA）如何影响饱和硬脂酸（SA）对人胰腺β细胞 NES2Y 细胞凋亡诱导过程中 p38 丝裂原活化蛋白激酶（MAPK）和细胞外信号调节激酶（ERK）通路以及 ER 应激信号通路的影响。我们证明，OA 能够抑制 SA 的所有作用。OA 单独对 NES2Y 细胞中测试的信号通路几乎没有影响或没有影响。因此，OA 抑制性干预 SA 诱导的凋亡信号的作用点似乎位于所讨论的信号通路的上游。
